Journal of microbiology, epidemiology and immunobiologyJournal of microbiology, epidemiology and immunobiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-7613Central Research Institute for Epidemiology13962ArticlesСтатьиReview ArticleFROM MOLECULAR TO GENOMIC AND METAGENOMIC EPIDEMIOLOGYОТ МОЛЕКУЛЯРНОЙ К ГЕНОМНОЙ И МЕТАГЕНОМНОЙ ЭПИДЕМИОЛОГИИZhebrunA. BЖебрунА. БPasteur Research Institute of Epidemiology and MicrobiologyНИИ эпидемиологии и микробиологии им. Пастера150620142014913NO3 (2014)№3 (2014)9110009062023Received:09062023Published:15062014Copyright ©; 2014, Zhebrun A.B.Copyright ©; 2014, Жебрун А.Б.2014Zhebrun A.B.Жебрун А.Б.https://creativecommons.org/licenses/by/4.0https://microbiol.crie.ru/jour/article/view/13962

The notion «molecular epidemiology» was introduced into scientific literature by Kilburn E. et al. in 1973. The first period of development of infectious diseases molecular epidemiology may be called «genotypic» (1980-1990s). During this period methodology of molecular marking of pathogens for purposes of monitoring of their spread and outbreak detection (novel nomenclature of diphtheria corynebacteria based on ribotyping; international network PulseNet for monitoring food source infections; international database of tuberculosis mycobacteria spoligotypes) was created. The second - «genomic» period started in the 2000s. Molecular epidemiology rapidly went through single markers (genotypes or single genes) to deciphering the whole genome of pathoge»mobileome», «resistome», «virulome» etc. took an important place in the studies of emerging and pandemic infections. Knowledge on genetic mechanisms leading to emergence and global dissemination of novel pathogens give molecular epidemiology its own scientific content and transforms it from a methodical approach to an independent field of epidemiology. The third - «metagenomic» period starts nowadays based on meta-genomic approach that allows to determine the whole set of genomes in the studied sample without the cultivation procedure. In the short term this would lead to a change of a century-long paradigm of diagnostics and control of infections: instead of search of separate (key) pathogens - characteristics of the full specter of microorganisms in the material from patients and environmental samples with its identification up to any taxonomic depth. In the systems of regional and global epidemiologic control a universal monitoring of all known and re-emerging pathogens with construction and maintenance of metagenomic passports of human habitats will be realized.

Понятие «молекулярная эпидемиология» введено в научную литературу Kilburn E. et al. в 1973 году. Первый период в развитии молекулярной зпидемиологии инфекционных болезней может быть назван «генотипическим» (80-90-е годы ХХ века). В ходе его создавалась методология молекулярного маркирования патогенов для целей мониторинга их распространения и детекции вспышек (новая номенклатура коринебактерий дифтерии на основе риботипирования; международная сеть PulseNet для мониторинга инфекций пищевого происхождения; международная база данных сполиготипов микобактерий туберкулеза). Второй - «геномный» период начался в нулевые годы ХХ! века. Молекулярная эпидемиология быстро прошла путь от единичных маркеров (генотипов, или отдельных генов) до расшифровки полного генома патогенов. Геномный подход и понятия «пангеном», «коровый геном», «мобилеом», «резистом», «вирулом» и др. заняли важное место в изучении эмержентных и пандемичных инфекций. Знания о генетических механизмах, ведущих к возникновению и глобальной диссеминации новых патогенов, придают молекулярной эпидемиологии собственное научное содержание и превращают ее из методического направления в самостоятельную отрасль эпидемиологии. Третий - «метагеномный» период начинается в наши дни на базе метагеномного подхода, который позволяет без процедуры культивирования определять всю совокупность геномов в исследуемом образце. В ближайшей перспективе это приведет к смене вековой парадигмы диагностики и надзора за инфекциями: вместо поиска отдельных (целевых) патогенов - к характеристике полного спектра микроорганизмов в материале от больных или пробах внешней среды с его идентификацией на любую таксономическую глубину. В системах регионального и глобального эпидемиологического надзора будет реализован всеобъемлющий мониторинг всех известных и вновь появляющихся патогенов с построением и ведением метагеномных паспортов сред обитания человека.

molecular epidemiologygenomic epidemiologymetagenomic epidemiologygenotypingepidemiologic controlмолекулярная эпидемиологиягеномная эпидемиологияметагеномная эпидемиологиягенотипированиеэпидемиологический надзорЛаст Дж.М. (ред.). Эпидемиологический словарь. М., 2009.Львов Д.К., Забережный А.Д., Алипер Т.И. Вирусы гриппа: события и прогнозы. Природа. 2006, (6): 3-13.Парахонский А.П., Венглинская Е.А. Интеграция и дифференциация наук, их связь с образованием. Успехи современного естествознания. 2009, 9: 86-87.Aarestrup FM., Brown E.W, Detter C. et al. Integrating Genome-based Informatics to Modernize Global Disease Monitoring, Information Sharing, and Response. EID J. 2012, 18 (11). Available at: http://dx.doi.org/10.3201/eid1811.120453 (Accessed 20 November 2013).Aguileta G., Refregier G., Yockteng R. et al. Rapidly evolving genes in pathogens: Methods for detecting positive selection and examples among fungi, bacteria, viruses and protists. Infection, Genetics and Evolution. 2009, 9 (4): 656-670.Beall B., Facklam R., Thompson T. Sequencing emm-specific PCR products for routine and accurate typing of group A streptococci. J. Clin. Microbiol. 1996, 34 (4): 953-958.Brudey K., Driscoll J.R., Rigouts L. et al. Mycobacterium tuberculosis complex genetic diversity : mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology. BMC Microbiol. 2006, 6 (1): 23-30.Caugant D.A. (ed.). Molecular Epidemiology ofMicroorganisms (Methods and Protocols). Humana Press, 2009.Dorman J.S., Introduction to Molecular Epidemiology. Avaliable at: www.pitt.edu/~super4/ 33011-34001/33891. ppt (Accessed 15 November 2013).Eurosurveillance. 2013, 18 (3, 4): 51-56.Enright M.C., Spratt B.G. A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease. Microbiology. 1998, 144 (11): 3049-3060.Foulongne V, Michaux-Charachon S., Jumas-Bilak E. et al. Strategies for bacterial virulence genes identification. Pathol. Biol. (Paris). 2004, 52 (2): 104-114.Frank C., Werber D., Cramer J.P et al. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N. Engl. J. Med. 2011, 365 (19): 1771-1180.Foxman B., Riley L. Molecular Epidemiology: Focus on Infection. Am. J. Epidemiol. 2001, 153 (12): 1135-1141.Grenfell B.T., Pybus O.G., Gog J.R. et al. Unifying the epidemiological and evolutionary dynamics of pathogens. Science. 2004, 303 (5656): 327-332.Graham R.L., Baric R.S. Recombination, Reservoirs, and the Modular Spike: Mechanisms of Coronavirus Cross-Species Transmission. J. Virol. 2010, 84 (7): 3134-3146.Garten R.J., Davis C.T., Russell C.A. et al. Antigenic and Genetic Characteristics of the Early Isolates of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans. Science. 2009, 325 (5937): 197-201.Guan, Y., Zheng B.J., He Y.Q. et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science. 2003, 302: 276-278.Ghedin E., Sengamalay N.A., Shumway M. et al. Large-scale sequencing ofhuman influenza reveals the dynamic nature of viral genome evolution. Nature. 2005, 437:1162-1166.Garten R.J., Davis C.T., Russell C.A. et al. Antigenic and Genetic Characteristics of the Early Isolates of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in Humans. Science. 2009, 325 (5937): 197-201.Hunter D. The future of molecular epidemiology. Int. J. Epidemiology. 1999, 28: 1012-1014.Hao W, Allen YG., Jamieson F.B. et al. Phylogenetic incongruence in E. coli O104: understanding the evolutionary relationships of emerging pathogens in the face of homologous recombination. PloS one. 2012, 7 (4): e33971. Avaliable at: http://www.straininfo.net/publications/147247/ browser/doi;jsessionid=B136EB8390250967DB4B0ECDA7A004CE.straininfo1 (Accessed 20 November 2013).Handelsman J., Rondon M.R., Brady S. F. et al. Molecular biological access to the chemistry of unknown soil microbes: A new frontier for natural products. Chemistry Biology. 1998, 5 (10): 245249.Kilbourne E.D. The Molecular Epidemiology of Influenza. J. Infect. Dis. 1973, 127 (4): 478-487.Levin B.R., Lipsitch M., Bonhoeffer S. Population biology, evolution, and infectious disease: convergence and synthesis. Science. 1999, 283: 806-809.Last J.M. (ed.). A dictionary of epidemiology. Oxford, University Press, 2001.Lopez-Garsia P., Moreira D. Tracking microbial diversity through molecular and genomic ecology. Res. Microbiology. 2008, 159 (1): 67-73.Lepage P., Leclerc M.C., Joossens M. et al. A metagenomic insight into our gut's microbiome. Gut. 2013, 62: 146-158.Liu L. Li Y. Li S. et al. Comparison of Next-Generation Sequencing Systems. J. Biomed. Biotechnology. 2012: 1-11. Available at: http://www.hindawi.com/journals/bmri/2012/251364/ (Accessed 20 November 2013).Morand S., Beaudeau F., Cabaret J. (ed.). New frontiers of molecular epidemiology of infectious diseases. Springer, 2012.Maiden M.C., Bygraves J.A., Feil E. et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc. Natl. Acad. Sci. USA. 1998, 95 (6): 3140-3145.Medini D., Donati C., Tettelin H. et al. The microbial pan-genome. Curr. Opin. Genet. Dev. 2005, 15 (6): 589-594.Muellner P., Pleydell E., Pirie R. et al. Molecular-based surveillance of campylobacteriosis in New Zealand - from source attribution to genomic epidemiology. Euro Surveill. 2013, 18 (3). Available at: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20365 (Accessed 20 November 2013).Niesters H.G., Rossen.J.W, van der Avoort H. et al. Laboratory-based surveillance in the molecular era: the TYPENED model, a joint data-sharing platform for clinical and public health laboratories. Euro Surveill. 2013, 18 (4): 51-56.Nakamura S., Nakaya T., Iida T. Metagenomic analysis of bacterial infections by means of high-throughput DNA sequencing. Exp. Biol. Med. 2011, 236 (8): 968-971.Olsen G.J., Woese C.R., Overbeek R. The winds of (evolutionary) change: breathing new life into microbiology. J. Bacteriol. 1994, 176 (1): 1-6.Popovic T., Kombarova S.Y, Reeves M.W et al. Molecular epidemiology of diphtheria in Russia, 1985-1994. J. Infect. Dis. 1996, 174 (5): 1064-1072.Parkhill J., Wren B.W Bacterial epidemiology and biology - lessons from genome sequencing. Genome Biol. 2011, 12 (10): 230.Palm D., Johansson K., Ozin A., Friedrich A.W et al. Molecular epidemiology of human pathogens: how to translate breakthroughs into public health practice, Stockholm, November 2011. Euro Surveill. 2012, 17 (2). Available at: http://wwweurosurveillance.org/ViewArticle.aspx?ArticleId=20054 (Accessed 20 November 2013).Rothman N., Hainaut P., Schulte P. (ed.). Molecular Epidemiology: Principles and Practices. Media Centre - IARC News, IARC Scientific Publication, No 163, 2012.Rykkvin R., Kilander A., Dudman S.G., Hungnes O. Within-patient emergence of the influenza A(H1N1)pdm09 HA1 222G variant and clear association with severe disease, Norway. Euro Surveill. 2013, 18 (3): 3-13.Schulte P.A., Perera F.P. (ed.). Molecular epidemiology: principles and practices. San Diego, CA, Academic Press, 1993.Shpilberg O., Dorman J. S., Ferrell R.E. et al. The next stage: molecular epidemiology. J. Clin. Epidemiol. 1997, 50 (6): 633-638.Swaminathan B., Barrett T.J., Hunter S.B., Tauxe R.V. PulseNet: the molecular subtyping network for foodborne bacterial disease surveillance, United States. Emerg. Infect. Dis. 2001, 7 (3): 382389.Spratt B.G., Maiden M.C.J. Bacterial population structure and epidemiology. Phil. Trans. R. Soc. Lond. B. 1999, 354: 701-710.Sallis J.F., Owen N., Fotheringham M.J. Behavioral epidemiology: a systematic framework to classify phases of research on health promotion and disease prevention. Ann. Behav. Med. 2000, 22 (4): 294-298.Scheutz F., Nielsen E.M., Frimodt-Meller J. et al. Characteristics of the enteroaggregative Shiga toxin/verotoxin-producing Escherichia coli O104:H4 strain causing the outbreak of haemolytic uraemic syndrome in Germany, May to June 2011. Euro Surveill. 2011, 16 (24). Available at: http:// www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19889 (Accessed 20 November 2013).Struelens M.J., Brisse S. From molecular to genomic epidemiology: transforming surveillance and control of infectious diseases. Euro Surveill. 2013, 18 (4): 3-6.Sabat A.J., Budimir A., Nashev D. et al. Overview of molecular typing methods for outbreak detection and epidemiological surveillance. Euro Surveill. 2013, 18 (4): 17-31.The Human Microbiome Project Consortium. A framework for human microbiome research. Nature. 2012, 486: 215-221.Urwin R., Maiden M.C. Multi-locus sequence typing: a tool for global epidemiology. Trends Microbiol. 2003, 11 (10): 479-487.Wright G. D. The antibiotic resistome: the nexus of chemical and genetic diversity. Nature Rev. Microbiol. 2007, 5 (3): 175-186.Wylie K.M., Mihindukulasuriya K.A., Sodergren E. et al. Sequence Analysis of the Human Virome in Febrile and Afebrile Children. PLoS ONE. 2012, 7 (6). Avaliable at: http://www.plosone.org/ article/info%3Adoi%2F10.1371%2Fjournal.pone.0027735 (Accessed 20 November 2013).Xu J. Population genetics in the age of metagenomix: impact on investigations of viral, bacterial, archaeal and eukaryotic microbial communities. In: Xu J. Microbial population genetics. UK, Horizon Scientific Press, 2010: 189-204.